Although long known to be present in blood vessels, non-mast cell histamine has received little investigation over the years as a potential autocrine/paracrine factor in the vascular system. In view of extensive evidence. suggesting multiple important roles for histamine in vascular physiology and pathophysiology, the long-term goal of our research is to determine the function of non-mast cell histamine in blood vessels. The presently proposed research is designed to localize the source(s) of non-mast cell histamine within the vascular wall and initiate studies aimed at elucidating regulatory mechanisms of histamine synthesis and release from smooth muscle and/or endothelial cells. The specific aims are to test the hypotheses that: 1) rat aortic smooth muscle and/or endothelial cells contain and release histamine in response to the calcium ionophore, A23187; 2) A23187-induced histamine release is Ca2+-dependent and selected endogenous agonists known to increase [CA2+]i in rat aortic smooth muscle and/or endothelial cells can also stimulate release of histamine; and 3) agonist-induced release of histamine from rat aortic smooth muscle and/or endothelial cells involves exocytosis and/or is associated with increased histamine synthesis. The results obtained from this fundamental investigation should provide us with exciting, novel, basic information necessary for future investigation aimed at delineating the potential physiological/pathophysiological role(s) of locally derived non-mast cell histamine within the vascular wall.